Search results for "HMG-COA REDUCTASE"
showing 10 items of 34 documents
HMG-CoA reductase promotes protein prenylation and therefore is indispensible for T-cell survival.
2017
AbstractStatins are a well-established family of drugs that lower cholesterol levels via the competitive inhibition of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). In addition, the pleiotropic anti-inflammatory effects of statins on T cells make them attractive as therapeutic drugs in T-cell-driven autoimmune disorders. Since statins do not exclusively target HMGCR and thus might have varying effects on different cell types, we generated a new mouse strain allowing for the tissue-specific deletion of HMGCR. Deletion of HMGCR expression in T cells led to a severe decrease in their numbers with the remaining cells displaying an activated phenotype, with an increased pro…
Lipid-altering efficacy of ezetimibe/simvastatin 10/20 mg compared with rosuvastatin 10 mg in high-risk hypercholesterolaemic patients inadequately c…
2009
SUMMARY Aims: To evaluate the efficacy of switching from a previous statin monotherapy to ezetimibe ⁄simvastatin (EZE ⁄SIMVA) 10 ⁄20 mg vs. rosuvastatin (ROSUVA) 10 mg. Methods: In this randomised, double-blind study, 618 patients with documented hypercholesterolaemia [low-density lipoprotein cholesterol (LDL-C) ‡ 2.59 and £ 4.92 mmol ⁄l] and with high cardiovascular risk who were taking a stable daily dose of one of several statin medications for ‡ 6 weeks prior to the study randomisation visit entered a 6-week open-label stabilisation ⁄screening period during which they continued to receive their prestudy statin dose. Following stratification by study site and statin dose ⁄potency, patien…
Loss of the preconditioning effect of rosuvastatin during sustained therapy: a human in vivo study
2011
Studies have demonstrated that the acute administration of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors has protective effects in the setting of ischemia-reperfusion (IR). Previously, we demonstrated that a single dose of rosuvastatin prevented IR-induced endothelial dysfunction in humans through a cyclooxygenase-2-dependent mechanism. Whether the chronic administration of HMG-CoA reductase inhibitors provides similar protection remains controversial and is unknown in humans. Eighteen male volunteers were randomized to receive a single dose of rosuvastatin (20 mg) or placebo. Twenty-four hours later, endothelium-dependent, radial artery flow-mediated dilation (FMD) w…
Subcutaneous gonadotropin therapy in male patients with hypogonadotropic hypogonadism
1991
Objective The response to subcutaneous (SC) gonadotropin replacement therapy, using human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG) or hCG alone, was evaluated in male hypothalamic hypogonadism. Design Sixteen patients with hypothalamic hypogonadism were treated with gonadotropins for induction of puberty and normalization of spermatogenesis. The results were analyzed retrospectively. Setting The study was carried out in a clinical endocrinology department providing tertiary care and in private practices of endocrinology. Patients Eight patients with idiopathic hypogonadotropic hypogonadism and eight patients with Kallmann's syndrome in prepubertal or early pubert…
Coadministration of atorvastatin prevents nitroglycerin-induced endothelial dysfunction and nitrate tolerance in healthy humans.
2010
Objectives We aimed to assess whether concurrent administration of atorvastatin would modify the development of tolerance and endothelial dysfunction associated with sustained nitroglycerin (GTN) therapy in humans. Background Animal studies have demonstrated that administration of 3-hydroxy-3 methylglutaryl coenzyme A reductase inhibitors can protect against GTN-induced endothelial dysfunction and tolerance, likely through an antioxidant mechanism. Methods Thirty-six healthy male volunteers were randomized to receive continuous transdermal GTN (0.6 mg/h) and placebo, atorvastatin (80 mg/day) alone, or continuous transdermal GTN (0.6 mg/h) with concurrent atorvastatin (80 mg/day), all for 7 …
Cholesterol in Alzheimer’s Disease and other Amyloidogenic Disorders
2010
The complex association of cholesterol metabolism and Alzheimer’s disease is presented in depth, including the possible benefits to be gained from cholesterol-lowering statin therapy. Then follows a survey of the role of neuronal membrane cholesterol in Aβ pore formation and Aβ fibrillogenesis, together with the link with membrane raft domains and gangliosides. The contribution of structural studies to Aβ fibrillogenesis, using TEM and AFM, is given some emphasis. The role of apolipoprotein E and its isoforms, in particular ApoE4, in cholesterol and Aβ binding is presented, in relation to genetic risk factors for Alzheimer’s disease. Increasing evidence suggests that cholesterol oxidation p…
Lovastatin protects human endothelial cells from killing by ionizing radiation without impairing induction and repair of DNA double-strand breaks.
2006
Abstract Purpose: 3-hydroxy-3-methylglutaryl CoA reductase inhibitors (statins) are frequently used lipid-lowering drugs. Moreover, they are reported to exert pleiotropic effects on cellular stress responses, proliferation, and apoptosis. Whether statins affect the sensitivity of primary human cells to ionizing radiation (IR) is still unknown. The present study aims at answering this question. Experimental Design: The effect of lovastatin on IR-provoked cytotoxicity was analyzed in primary human umbilical vein endothelial cells (HUVEC). To this end, cell viability, proliferation, and apoptosis as well as DNA damage–related stress responses were investigated. Results: The data show that lova…
The HMG-CoA reductase inhibitor lovastatin protects cells from the antineoplastic drugs doxorubicin and etoposide
2002
Ras-homologous GTPases are involved in the regulation of genotoxic stress-induced gene expression and cell death. Since they need C-terminal isoprenylation for correct intracellular localization and function, we investigated whether depletion of cells from isopren precursor moieties using the HMG-CoA reductase inhibitor lovastatin affects cellular sensitivity to DNA damaging drugs. Here we show that lovastatin renders cells highly resistant to the tumor-therapeutic compound doxorubicin. Desensitization by lovastatin was reverted by co-treatment with GGPP indicating that inhibition of protein geranylgeranylation is involved in acquired doxorubicin resistance. Lovastatin does not influence ce…
Potential use of HMG-CoA reductase inhibitors (statins) as radioprotective agents
2011
HMG-CoA reductase inhibitors (statins) are widely used in the therapy of hypercholesterolemia. Apart from their lipid-lowering activity, they have pleiotropic effects that are attributed to the inhibition of regulatory proteins, including Ras-homologous (Rho) GTPases. Here, we discuss the potential usefulness of statins to prevent normal tissue damage provoked by radiotherapy. Statins reduce the mRNA expression of pro-inflammatory and pro-fibrotic cytokines stimulated by ionizing radiation in vitro and alleviate IR-induced inflammation and fibrosis in vivo. The currently available data indicate that statins accelerate the rapid repair of DNA double-strand breaks and, moreover, mitigate the …
Lovastatin protects human endothelial cells from the genotoxic and cytotoxic effects of the anticancer drugs doxorubicin and etoposide
2006
Background and purpose: 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are frequently used lipid-lowering drugs. Moreover, they exert pleiotropic effects on cellular stress responses and death. Here, we analysed whether lovastatin affects the sensitivity of primary human endothelial cells (HUVEC) to the anticancer drug doxorubicin. Experimental approach: We investigated whether pretreatment of HUVEC with low dose of lovastatin influences the cellular sensitivity to doxorubicin. To this end, cell viability, proliferation and apoptosis as well as DNA damage-triggered stress response were analysed. Key results: Lovastatin reduced the cytotoxic potency of doxorub…